Associations between STAT3 rs744166 Polymorphisms and Susceptibility to Ulcerative Colitis and Crohn's Disease: A Meta-Analysis

Abstract

BackgroundMany studies have investigated the associations between the signal transducer and activator of transcription 3 (STAT3) in the susceptibility to ulcerative colitis (UC) and Crohn's disease (CD). However, the results remain inconsistent. This meta-analysis determined the risk of STAT3 rs744166 polymorphism-conferred UC and CD susceptibility.Materials and MethodsElectronic databases, including PubMed, EMBASE and the Cochrane Library, were searched for all eligible studies that evaluated the association between STAT3 rs744166 polymorphisms with UC and CD risk up to August 21, 2014. The pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using fixed- or random-effects models.ResultsTwelve studies containing 10298 patients with CD, 4244 patients with UC and 11191 controls were included in this meta-analysis. The results indicated that the STAT3 rs744166 polymorphism was associated with CD and UC susceptibility (CD: GA+AA vs. GG, OR = 1.20, 95%CI, 1.11–1.30, I 2 = 0%, P unadjusted<0.00001, P Bonferroni<0.00005, P FDR<0.00001; UC: GA+AA vs. GG, OR = 1.21, 95%CI, 1.08–1.36, I 2 = 1%, P unadjusted = 0.001, P Bonferroni = 0.005, P FDR = 0.00125). In subgroup analyses by ethnicity, the significant association was found only among Caucasians. However, when grouped by age of onset, positive associations were found both among adults and children. In addition, when stratified by study design and genotyping methods, the risk of CD was significantly associated with the STAT3 rs744166 polymorphism in hospital-based and population-based groups and in SNP Array and SNPlex groups. For UC, significant associations were also found in population-based, PCR-RFLP and SNPlex groups. Moreover, these findings were sufficiently robust to withstand the Bonferroni correction and false discovery rate (FDR).ConclusionThis meta-analysis indicates that carriers of the STAT3 rs744166 ‘A’ allele have a significantly greater risk of CD and UC, especially among Caucasians.

Investigation of IL23R, JAK2, and STAT3 gene polymorphisms and gene–gene interactions in Crohn’s disease and ulcerative colitis in a Turkish population

“…A meta-analysis evaluating the rs744166 variant of STAT3 reported that the (A) allele was a risk factor for both UC and CD. In the meta-analysis which assessed 7 CD (4244 patients) and 5 UC (10298 patients) studies, it was reported that the (A) allele increased UC and CD susceptibility in those of Caucasian descent more, compared to other ethnic origins (21). In our study, though no genotypic or phenotypic association with UC was identified, the (TT) genotype of the polymorphism appeared to form a risk for CD.…”

“…In later polymorphism studies, it was shown that some increased the susceptibility for IBD. However, the results of the studies of different populations are insufficient and contradictory (21). For the rs744166 variant of STAT3, Ferguson et al (17) reported the (G) allele and (GG) genotype were protective against CD.…”

“…The RT-PCR procedure was completed using the PimerDesign®SNPsig Real-Time PCR mutation detection/allelic discrimination Kit (PrimerDesign Ltd.; Southampton, UK) in accordance with the manufacturer's protocol (23). The rs11209026 (G>A, R381Q) of the IL23R gene, rs10758669 (A>C) of the JAK2 gene, and rs3816769 (T>C), rs2293152 (G>C), rs744166 (C>T), rs957970 (C>T), and rs8074524 (C>T) of the STAT3 gene were examined in the obtained genomic DNA (16,17,(19)(20)(21). The prepared 20 μL PCR solution contained 10 μL PimerDesign®2xPrecision MasterMix, 1 μL Primer/probe mix, 4 μL water not containing ribonuclease and deoxyribonuclease, and 5 μL genomic DNA for each reaction.…”

“…It is thought that the IL23/IL23R signal pathway may play a central role in the pathogenesis of IBD. Though there are studies showing that IL23R, JAK2, and STAT3 cause susceptibility to UC and CD in different ethnic groups, the results are not consistent (6,13,(15)(16)(17)(18)(19)(20)(21). The reason for this discrepancy may be that IBD in different ethnic communities may appear through different predominant mechanisms.…”

Characterization analysis and heavy metal‐binding properties of CsMTL3 in Escherichia coli

“…In addition, the highly conserved CxCxxxCxCxxCxC motif of plant MTs was also found in CsMTL3 [9]. The type 2 MT family is characterized by conserved N-terminal sequences, for example, MSCCGGN, MSCCGGS, MSSCCGGN, and MSCCSGN [9,32,33,40,41]. By contrast, MST-CGN, MSSTCG, and MSSSCG sequences are found in the N terminus of the type 3 MTs (Fig.…”